4 Questions for Immunotherapy Pioneer Dr. James Allison
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ancer. It's a diagnosis that no one ever wants to hear.
But thanks to innovations in treatment, there is more hope than ever before. And one of the most significant breakthroughs in cancer treatment has been immunotherapy, which harnesses a patient's own immune system to fight the disease.
After decades of dedicated oncology and immunotherapy research, James Allison, Ph.D., director of the Parker Institute for Cancer Immunotherapy in San Francisco and the executive director of the Immunotherapy Platform at MD Anderson Cancer Center in Houston, discovered a new way to recruit the immune system to attack solid tumor cancers.
His discoveries around T cell responses garnered him the 2018 Dr. Paul Janssen Award for Biomedical Research, placing him among just 15 other scientists who have won the award since 2006. The award was established to honor the work of Paul Janssen, founder of Janssen Pharmaceutica, by recognizing scientists whose work has helped improve public health.
We sat down with Dr. Allison to learn more about his groundbreaking work, which also just brought him another prestigious accolade—the 2018 Nobel Prize in Physiology or Medicine.
What inspired your career in cancer research?
When I was a kid, my father wanted me to become a doctor like him. But when I had the chance to do a summer tutorial and laboratory work as a junior in high school, I got the research bug—and then my interest was further piqued by a course on immunology.
In the class I took, we learned about T cells—a type of white blood cell that protects against infection. Not much was known about T cells at the time, and I was curious to find out more. I figured if we could understand how T cells work, we could discover how to kill cancer cells without the destructive side effects of radiation and chemotherapy.
Plus, cancer was always in the back of my mind for personal reasons. My mother died of lymphoma when I was 10 years old, and two uncles also passed away from cancer when I was young.
I also have a history with the disease: I’ve been diagnosed with prostate cancer and melanoma, which were both caught early. And I'm currently undergoing immunotherapy for early stage bladder cancer.
What makes your research so revolutionary?
In the past, researchers thought the job of T cells was to kill cancer, similar to how chemotherapy works. Early attempts to harness the immune system involved creating therapeutic vaccines derived from cancer cell components to try to get T cells to attack the tumor.
My approach was very different in that it basically ignored the tumor and instead focused on figuring out how to block signals that inhibited the powers of T cells.
Through my research, I discovered a protein on the T cell, called CD28, which acts as its gas pedal, as well as a receptor on the T cell, called CTLA-4, which acts as its brakes. Basically, CD28 and CTLA-4 turn the T cells on and off like a car.
No one realized this braking mechanism needed to be turned off in order for the immune system to unleash a powerful attack on cancer. With this discovery, we were able to figure out how to utilize this switchlike ability to temporarily disable the brakes and create treatments that effectively target cancer.
I'm so humbled to get a prize in Paul Janssen's honor. Like me, Paul Janssen was a man of the basic sciences, who studied physics, chemistry and biology before medicine. Sometimes they get neglected by funding, but new drugs and breakthroughs do come from studying chemistry, biology and physics.Share
What has been the most rewarding part of your research?
It has been amazing to see how my research has affected the lives of patients.
One stands out in particular: Sharon Belvin was in her early 20s and had metastatic melanoma. Every available treatment to her had failed, so she got involved in early clinical trials of immunotherapy treatments.
It was the last chance she had to survive—it was either that or go into hospice care.
A few months after starting the immunotherapy treatment, she bounced back. One year later, she was declared tumor-free. At the time, I was working at Memorial Sloan Kettering Cancer Center, and saw her after she met with her doctors there. She hugged me and said she had been convinced that her doctors were going to tell her she had relapsed—but the exact opposite had happened.
It's hard to describe the impact this made—she was the first patient I'd met who had been affected by my work.
What does winning this award mean to you?
I'm so humbled to get a prize in Paul Janssen's honor. Like me, Paul Janssen was a man of the basic sciences, who studied physics, chemistry and biology before medicine.
I really want people to know the importance of basic sciences and support them, too. Sometimes they get neglected by funding, but new drugs and breakthroughs do come from studying chemistry, biology and physics.
For example, if I hadn't been so focused on the very basic components of the T cell, I never would have made my discoveries that helped revolutionize immunotherapy.
I think that immunotherapy is going to become part of the standard of care for different types of cancer. The next step in my research is finding out why certain patients don’t respond to this treatment. Once we can figure that out, we can greatly improve the quality of this treatment and see even more patients survive.
Meet Sharon Belvin—the metastatic melanoma survivor Dr. Allison mentions—who shares her personal cancer journey, and the amazing impact he had on her life, in this video.